Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs

Abstract

Context: Herb-drug interactions are a serious problem especially for drugs with a narrow therapeutic index, taking into consideration that herbal medicines are commonly used in various parts of the world. Objective: The present study investigates the effect of fenugreek, garden cress, and black seed on the pharmacokinetics of theophylline in beagle dogs. Materials and methods: Beagle dogs received theophylline (200mg) orally and blood samples were withdrawn at different time intervals (0.33, 0.66, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, and 30h). After a suitable washout period, each herb was given orally at doses of 25, 7.5, and 2.5g, twice daily for 7 d. On the eighth day, theophylline was re-administrated orally and blood samples were collected. Plasma concentrations of theophylline were determined using HPLC and pharmacokinetic parameters were calculated using a non-compartmental analysis. Results: Treatment with fenugreek (25g, orally) lead to a decrease in Cmax and AUC0-t of theophylline of about 28% (p<0.05) and 22% (p<0.05), respectively, with no significant changes in T1/2 compared with the baseline values. Garden cress caused a decrease in Cmax to a lesser extent and delayed Tmax of theophylline (2.10±0.24h versus 3.40±0.74h), while AUC0-∞ increased by 37.44%. No significant effect was observed for the black seed treatment on theophylline disposition as measured by Cmax, Tmax, AUC0-∞, and CL/F. Discussion and conclusion: The concurrent use of fenugreek or garden cress alters theophylline pharmacokinetic behavior in an animal model. This could represent a modulation in cytochrome P450 activity, which is responsible for theophylline metabolism in beagle dogs. Further confirmation of these results in humans will warrant changes in theophylline dosing before the co-administration of such herbs.